Applying the RatWalker System for Gait Analysis in a Genetic Rat Model of Parkinson's Disease

Parkinson's disease relevant pathological features are manifested in male Pink1/Parkin deficient rats

“…Gait disturbances are a defining feature of PD occurring early during disease course and include decreased arm swing, slower walking speed, and shorter steps ( Zanardi et al, 2021 ). We previously reported gait abnormalities in Pink1/Parkin dKO rats at an early age, 2 months ( Stauch et al, 2021 ). Here, to evaluate the age-related progression of the gait changes, we quantitatively examined the walking behavior in freely walking Pink1/Parkin dKO and WT rats at 1, 3, 6, 9, and 12 months of age using an optical touch sensor based on frustrated total internal reflection (FTIR).…”

“…A RatWalker system was developed by our group to measure gait in rats ( Stauch et al, 2021 ) based on adaptations to the MouseWalker system developed to measure gait in mice ( Mendes et al, 2015 ). Briefly, the rat home cage was placed at the end of the walker so the rats could walk freely on the walking floor toward their home cage without turning.…”

Pink1/Parkin deficiency alters circulating lymphocyte populations and increases platelet-T cell aggregates in rats

“…Our prior study using isolated PBMCs revealed increased CD4 + T cells and decreased CD8 + T cells in Pink1/Parkin dKO rats at 12 months 25 . To assess the effects of Pink1 and Parkin alone as well as age on the circulating lymphocyte populations in rats, we isolated PBMCs from Pink1 sKO, Parkin sKO, and Pink1/Parkin dKO rats at 5-6 months of age, an age when Pink1 sKO and Pink1/Parkin dKO rats exhibit motor symptoms 17,22,24 . We found that the percentage of CD3 + T cells was higher in Pink1 sKO, Parkin sKO, and Pink1/Parkin dKO rats as compared to WT controls.…”

“…Rats with targeted disruption of the Park6 gene (Pink1 single knockout, sKO), the Park2 gene (Parkin sKO), and the background strain (Long Evans Hooded) were obtained from SAGE Labs (now Inotiv) 17 . Pink1/Parkin double KO (dKO) rats were generated in our lab from the sKO rats as described previously 24,25 . The rats were maintained on a 12-hour light/dark cycle in a temperature-controlled environment with free access to standard rat chow and water.…”

“…Parkin sKO rats appear resistant to motor impairment and nigrostriatal DA neurodegeneration up to 8 months of age 17 but do show abnormalities in DA metabolites 20 . We generated a combined Pink1/Parkin double knockout rat (dKO), which display a PD-relevant phenotype, including gait abnormalities and tremor as well as α-synuclein aggregation in the striatum that coincides with loss of nigral neurons 24,25 . Indeed, similar to animal models, the phenotypes of PD are diverse in humans, and characterizing early-onset PD is challenging in humans due to differential patterns of symptom manifestation, inconsistent age of disease onset, and environmental variability.…”